PB1964: RELATIONSHIP BETWEEN SIRT1-7 AND SELECTED MIRNAS EXPRESSIONS IN MYELOMA/LYMPHOMA PATIENTS IN DIFFERENT REMISSION STATUS.
Authors: M. Nowicki, A. Wierzbowska, E. Stec-Martyna, D. Kulczycka-Wojdala, G. Nowicki, A. Szmigielska-Kapłon
Journal: HemaSphere (2022)

Background: Sirtuins are members of the NAD+-dependent class III histone deacetylase group, which participate in the post-translational modification of proteins. MicroRNAs (miRNAs) are a class of small (19-25 nucleotides), endogenous RNA which play a significant role in regulation of gene expressions. Both molecules are engaged in cell proliferation, differentiation, stress response, apoptosis and hematopoietic stem cells (HSC) fate during mobilization and homing after auto-HSCT. Aims: The aim of the study was to investigate the association between SIRT1-SIRT7 and selected miRNAs on the day of first apheresis and the depth of myeloma/lymphoma response (CR versus not CR before mobilization regimen) in patients with lymphoproliferative malignancies during HSC mobilization for autologous transplantation. Methods: Forty nine patients were enrolled in the study (25 F, 24 M). The median (Me) age was 60 years. The investigated group consisted of thirty-three multiple myeloma (MM), seven non-Hodgkin lymphoma (NHL) and four Hodgkin lymphoma (HL) patients. Sirtuins and miRNAs (miRNA-15a, miRNA-16, miRNA-34a miRNA-126, miRNA-146a, miRNA-223 and miRNA-155) expression was evaluated in peripheral blood (PB). The blood serum samples were collected at two time points: before hematopoietic stem cell mobilization chemotherapy (day 0) and on the day of the first apheresis (day A). SIRT1-SIRT7 expression was evaluated by Droplet Digital PCR method while the miRNAs level was evaluated by Real Time PCR method. Results: To evaluate the influence of miRNA expression on the sirtuins level after mobilization, patients were divided into “high” (n=25) and “low” (n=24) expression groups according to median miRNA levels on day A (above and below median). The group of miRNA-34a “high expressors” had upregulated level of SIRT7 than “high expressors” (Me = 189.01 vs. 110.72 copies/200µL, p=0.03). The group of miRNA-223 “high expressors” had upregulated level of SIRT3, than “high expressors” (Me = 357.43 vs. 157.12 copies/200µL, p=0.04). Patients mobilized with chemotherapy and G-CSF (n = 44) were divided into CR (n = 10) and non-CR (n = 34) groups. On day A, a positive correlation was noticed between SIRT1, SIRT2, SIRT3, and SIRT6 level and miRNA-126 expression in non-CR group (R = 0.35, p=0.04), (R = 0.41, p=0.01), (R = 0.38, p=0.02), (R = 0.36, p=0.04) respectively. Additionally, a positive correlation was found between SIRT1, SIRT2, SIRT3, SIRT6 and SIRT7 concentration and miRNA-223 in non-CR group (R = 0.44, p=0.008), (R = 0.44, p-0.01), (R = 0.48, p=0.004), (R = 0.45, p=0.008), (R = 0.36, p=0.04) respectively. We found no correlation between sirtuins and miRNAs expression in patients in CR remission status. Image:Summary/Conclusion: Mutal reactions between sirtuins and miRNAs may influence the hematopoietic landscape during HSC mobilization and differ depending on the depth of myeloma/lymphoma response. Chemotherapy combined with G-CSF stimulation causes inflammation associated with intense angiogenesis and disruption of signaling pathways associated with HSC motility. These processes can be regulated by miRNA-34a, miRNA-126, miRNA-223 and selected sirtuins. The lack of correlation between miRNA expression and sirtuins in the CR group may be associated with a small number of patients.